Haemophilus ducreyi is the etiologic agent of chancroid. This sexually transmitted disease is predominantly found in developing countries, but it has been increasing in frequency in the United States. H. ducreyi has been implicated in the heterosexual transmission of Human Immunodeficiency Virus (HIV) in Africa. The pathogenicity and virulence of H. ducreyi remains poorly understood. Although only limited data exists concerning the lipooligosaccharides (LOS) of H. ducreyi, these studies suggest that the LOS may play an important role in the disease process. In a recent report, it has been shown that the typical lesions seen in the mouse model for H. ducreyi virulence can be produced by heat-killed organisms and purified LOS. The LOS of this organism has characteristics similar to other gram negative non-enteric mucosal pathogens, such as Neisseria meningitidis and Neisseria gonorrhoeae. Some strains of N. meningitidis and many strains of N. gonorrhoeae express an epitope(s) on their LOS that is immunochemically similar to a precursor of the human I erythrocyte antigen. This human antigen is found on red blood cells, neutrophils and in mucin. Our laboratory has recently demonstrated that this epitope(s) is present on the LOS of H. ducreyi. The organism may utilize these LOS epitopes as a form of molecular mimicry to evade host defense mechanisms.
The aim of this proposal is to test the hypothesis that the lipooligosaccharides (LOS) of Haemophilus ducreyi play an important role in the pathogenesis of chancroid. We believe that the oligosaccharide portion of the LOS contains epitopes which mimic human antigens and this mimicry may be an important factor in the ability of this organism to escape the immune response, while the lipid A moiety of the LOS is a primary factor in the cutaneous pathology of this infection. We will test these by: 1) Using monoclonal and polyclonal antibodies to define the antigenic and epitopic structure present on LOS's of H. ducreyi and to determine whether these antigens and epitopes play a role in molecular mimicry. 2) The elucidation of the mechanism mediating the biology effects of H. ducreyi LOS on the skin. 3) The development of isogenic LOS mutants from a wild type H. ducreyi strain by pyocin selection, chemical mutagenesis, or transposon insertion mutagenesis.
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